First medical product cleared in U.S. for use on certain injuries caused by sulfur mustard

The U.S. government reached a milestone in its long-standing efforts to defend the country against potential use of chemical weapons: the first U.S. Food and Drug Administration (FDA) clearance of a product to manage certain blister injuries caused by sulfur mustard, commonly known as mustard gas.

“Our top priority is saving lives during national emergencies. To do so, we must make safe and effective medical products for all the illnesses and injuries stemming from the serious health security threats confronting our nation,” said Robert Kadlec, M.D., Assistant Secretary for Preparedness and Response (ASPR) at U.S. Department of Health and Human Services. “This product clearance is the latest step in delivering on that promise to the American people.”

The ASPR’s Biomedical Advanced Research and Development Authority (BARDA) provided technical expertise and funding to support the studies necessary to show that the product, Silverlon, is appropriate for use on first- and second-degree skin burns caused by exposure to sulfur mustard.

“Chemical weapons like sulfur mustard cause horrific, painful, and life-altering injuries, yet in the 100-year history of sulfur mustard use, no medical countermeasures existed – until now,” added BARDA Director Rick Bright, Ph.D. “At BARDA, we are excited to have supported the first cleared product for use on skin injuries caused by sulfur mustard. This clearance exemplifies BARDA’s ongoing commitment to our partners and the nation as we seek out promising technologies and products to improve our nation’s health security and protect Americans.”

Argentum Medical, LLC, has received FDA clearances for multiple indications for Silverlon since 2003 and in that time the wound dressing has been used extensively by the U.S. military to treat burn and blast wounds. Silverlon dressings also are used widely by the healthcare and first responder communities.

“The FDA plays an important role in preparing our nation for a range of threats, including chemical, biological, radiological, and nuclear threats, providing guidance and support for the development of medical countermeasures that can be used safely, effectively and reliably during public health emergencies,” said Acting FDA Commissioner Ned Sharpless, M.D. “The expanded indication for this first-of-its-kind wound contact dressing to include management of certain injuries caused by sulfur mustard vapor exposure demonstrates our commitment to working closely with our federal partners, including BARDA, to expedite the availability of medical countermeasures essential for managing responses to chemical weapons attacks in both civilian and battlefield settings.”

BARDA’s support for this additional indication began in 2013 as part of the federal government’s effort to repurpose approved drugs and medical products to save lives and reduce injury in an attack on the United States.

This multi-purpose approach has proven to be cost-effective in preparing mass casualty emergencies from chemical, biological, and radiological agents. Repurposing products in widespread use additionally ensures first responders have a familiar product to use in a time of crisis.

Beginning in 2015, BARDA used Project BioShield authorities and the Project BioShield Special Reserve Fund to purchase Silverlon for the Strategy National Stockpile as part of BARDA’s burn countermeasure program. BARDA continues to work with Argentum on studies necessary for FDA clearance of Silverlon for use on radiation burns.

Silverlon is a silver-plated nylon dressing available commercially and used widely to aid in the management of acute skin wounds and first- and second-degree thermal burns. The silver plating helps kill bacteria within the dressing, and one dressing can be used for up to seven days. This allows for fewer dressing changes, which reduces the burden on caregivers and minimizes the pain and damage that would occur if the wound was disturbed.

Sulfur mustard was first used as a chemical weapon in World War I and can be released into the air, food or water. More recently the chemical was used in the Iran-Iraq war and in the Syrian Civil War.

“……Tragedy struck in Imo State on Monday after fumes from a generator left 10 guests who attended a traditional wedding dead…….[N]o fewer than 30 other guests were on life support in different hospitals in the Ikeduru and Mbaitoli Local Government Areas of the state as a result of the fumes they inhaled from the generator…..”

“……an underground railroad was being constructed beneath the city streets. Metal sheets were put down in place of asphalt to cover holes in certain sections of downtown roads during the construction.

At about 7:30 a.m., during a busy rush hour, a large explosion rumbled beneath the streets, blasting the metal sheets high into the air. Flames shot out from underground, some 150 feet high, throughout a 300-yard area. Cars were transformed into fireballs and one was reported to have been thrown 30 feet into the air. Some pedestrians in the area were enveloped by fire; others further away were blown to the ground. Flaming debris hit people up to half of a mile away. The final death toll was 110, with hundreds injured……”

“……either the train was unable to pull the overloaded freight cars up the slope or the train stopped to wait for a train descending in the opposite direction. In any case, the train sat idling in the tunnel for more than 30 minutes. While this might not have posed a severe danger in some circumstances, the train’s locomotives were burning low-grade coal substitutes because high-grade coal was hard to obtain during the war and the coal substitutes produced an excess of odorless and toxic carbon monoxide.

Approximately 520 of the train’s passengers were asphyxiated by the carbon monoxide as they sat in the train…..”

“….When workers opened the wrong pipeline on February 24, highly combustible octane gas poured into the ditches of Vila Soco. Soon after midnight, an explosion was sparked, and a fireball ripped through the favela. Some homes were literally thrown hundreds of feet into the air; others were instantly incinerated. The temperature at the heart of the fireball was estimated at 1,800 degrees Fahrenheit…..”

**Meticulous attention to standard protocols for personal protection, recognizing toxidromes, and treating patients
continues to be the best way to prepare for and respond to chemical agent exposures**

Purpose
This document provides a quick refresher on standard protocols for recognizing, treating, and protecting yourself from nerve agent exposures. Comprehensive follow-up guidance for Law Enforcement, Fire, EMS, HazMat, and Hospital-Based First Receivers incorporating lessons learned and best practices from the recent United Kingdom incidents will be forthcoming.

Background
Nerve agents are extremely toxic chemical warfare agents. Several nerve agents exist and are generally categorized as either
“high volatility” or “low volatility” chemicals, a measure of how likely they are to disperse in air. A high volatility nerve agent (easily dispersed in air) means that the exposure is likely to occur from breathing in its vapors resulting in the rapid onset of symptoms.
A low volatility nerve agent (not easily dispersed in air) typically gets absorbed through the skin and has a delayed onset of signs
and symptoms. An example of a high volatility nerve agent is sarin, whereas VX is a low volatility agent. In the body, a nerve
agent exerts its effects by inhibiting an enzyme (acetylcholinesterase), resulting in acute illness – specifically, cholinergic crisis.
Organophosphorus or carbamate pesticides produce similar effects to nerve agents.

KEY DISTINCTION BETWEEN NERVE AGENT POISONING AND OPIOID POISONING IS “SLUDGE” OR “DUMBBELS.”

Detection (If you strongly suspect a nerve agent)
•Contact HazMat or special operations teams
•Notify the local FBI Field Office WMD coordinator

Personal Protective Equipment (PPE)
•Emergency responders should have the proper training and education to work with hazardous materials.
•Those providing or assisting with patient care including decontamination should follow institutional policy for a chemical incident, wearing a recommended chemical protective suit, gloves, boots, and respiratory protection to prevent any secondary exposure from patients or objects.
•After patient decontamination is complete, providers should wear a gown and a double layer of nitrile gloves during
patient contact.

Patient Decontamination
•A person potentially exposed to a nerve agent should be decontaminated whether they develop signs of acute illness or not.
•Removal of clothing is a vital step to reduce ongoing and secondary exposure. Responders should pay particular attention to the risk of secondary exposure during clothing removal. Double bagging removed clothing is ideal.
•Wiping skin with a paper towel, dry wipe, or other cloth will also contribute to effective decontamination. This dry decontamination step can be performed by patients themselves and, along with clothing removal, should be done as early as possible.
•If contamination with liquid agent is suspected, patients should be decontaminated with water, ideally with a high-volume, low-pressure shower, including soap if available, gentle rubbing with a soft cloth or sponge, and active drying with a clean towel after the shower.
•If Reactive Skin Decontamination Lotion (RSDL) is available, it is recommended for spot decontamination.

Treatment*
•Nerve agent toxicity is the result of excessive acetylcholine, causing cholinergic crisis. Therapy focuses on treating the excessive secretions and bronchospasm with anticholinergic medications such as atropine with dosing titrated to respiratory secretions and airway resistance. Pralidoxime chloride (2-PAM Cl), a specific nerve agent antidote, augments the primary therapy of atropine; continuous infusions may be beneficial.
•Seizures should be managed with escalating doses of benzodiazepines (midazolam, lorazepam, or diazepam).
All patients, even without convulsions, who meet the severe criteria should be treated with midazolam, lorazepam,
or diazepam 10 mg IV/IM/IO. A pediatric patient in this setting is defined as an individual less than 18 years old
AND with an ideal body weight (IBW) of ≤ 40 kg. If IBW is > 40 kg, adult medication and dosing are more appropriate. For patients under 40 kg, use midazolam only: 0-13 kg –70 mcg/kg, >13-40 kg – 5 mg.
•Autoinjectors (AI) are a convenient means of rapidly administering drugs to treat nerve agent exposure, which may be especially useful pre-hospital or at a hospital managing a large number of patients. However, only certain drugs in specific doses are available in autoinjectors: DuoDote or Antidote Treatment Nerve Agent Autoinjector (ATNAA) or Mark 1 kit (atropine 2 mg/2-PAM Cl 600 mg); atropine 2 mg, 1 mg, or 0.5 mg; 2-PAM Cl 600 mg; diazepam 10 mg.

Repeat atropine (2 mg IV/IM) at 5- 10 minute intervals until secretions have diminished and breathing is comfortable or airway resistance has returned to near normal.

Specific Pediatric Considerations
For pediatric patients, existing autoinjectors may provide more than the recommended doses of atropine and
pralidoxime. The reference below provides a strategy to mitigate this issue if time and resources allow. This method allows you to discharge the contents of autoinjectors and dilute the drug to prepare the proper dose. Expert opinion would still recommend that, given the benefit compared to the possible harm in delaying treatment, severe patients should be treated with autoinjectors even if they provide doses above recommendations.
Corvino TF, Nahata MC, Angelos MG, Tschampel MM, Morosco RS, Zerkle J, Nelson RN. Availability, stability, and sterility of pralidoxime for mass casualty use. Ann Emerg Med. 2006 Mar; 47(3):272-7.

Additional Considerations
•If faced with a mass casualty incident and if pharmaceutical therapies become exhausted, consider contingency medical countermeasures at your discretion.
•Poison Control Centers provide 24-hour-a-day patient care support at 1-800-222-1222.
•The Secretary of Health and Human Services issued a declaration, effective April 11, 2017, under the Public Readiness and Emergency Preparedness Act (PREP Act) to provide liability immunity to certain individuals and entities against any claim of loss relating to the use of medical countermeasures against nerve agents, given certain conditions are met:
https://www.federalregister.gov/documents/2017/05/10/2017-09455/nerve-agents-and-certain-insecticides-organophosphorous-andor-carbamate-countermeasures
Other Resources
U.S. Department of Health and Human Services
Centers for Disease Control and Prevention /
Agency for Toxic Substances and Disease Registry
https://emergency.cdc.gov/agent/nerve/index.asp
https://www.atsdr.cdc.gov/mmg/mmg.asp?id=523&tid=93
Office of the Assistant Secretary for Preparedness and Response
https://chemm.nlm.nih.gov/na_hospital_mmg.htm
Personal Protective Equipment
U.S. Department of Labor
Occupational Safety and Health Administration
https://www.osha.gov/Publications/OSHA3370-protecting-EMS-respondersSM.pdf
https://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=standards&p_id=9765
Patient Decontamination
U.S. Departments of Health and Human Services and Homeland Security
https://www.phe.gov/Preparedness/responders/Pages/patientdecon.aspx
General
U.S. Department of Health and Human Services
Office of the Assistant Secretary for Preparedness and Response
https://asprtracie.hhs.gov/
National Fire Protection Association
https://www.nfpa.org/codes-and-standards/all-codes-and-standards/list-of-codes-and-standards/detail?code=473

Centers for Disease Control and Prevention (CDC) sent this bulletin at 09/16/2018 02:56 PM EDT

CDC issued the following Health Alert Network (HAN) Health Advisory on September 16, 2018. You are receiving this information because you subscribe to COCA email updates. If a colleague forwarded this email to you, yet you would like to receive future updates directly from COCA, click here.

If you have any questions about this or other clinical issues, please e-mail coca@cdc.gov

On behalf of the Clinician Outreach and Communication Activity (COCA)
Centers for Disease Control and Prevention (CDC)
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Summary
The Centers for Disease Control and Prevention (CDC) is reminding clinicians seeing patients from the areas affected by Hurricane Florence to maintain a high index of suspicion for CO poisoning. Other people who may be exposed to the same CO source may need to be identified and assessed.

The signs and symptoms of CO exposure are variable and nonspecific. A tension-type headache is the most common symptom of mild CO poisoning. Other symptoms may include dizziness, flu-like symptoms without a fever, drowsiness, chest pain, and altered mental status.

Although CO poisoning can be fatal to anyone, children, pregnant women, the unborn, persons with sickle cell disease, older adults, and persons with chronic illness (e.g., heart or lung disease) are particularly vulnerable.

Background
High winds and heavy rain from Hurricane Florence began affecting the southeastern U.S. around September 12, 2018. Impact on the southeast coast and inland led to thousands of people without power. Those without power may turn to alternate power sources such as gasoline generators and may use propane or charcoal grills for cooking. If used or placed improperly, these sources can lead to CO build up inside buildings, garages, or campers and poison the people and animals inside.

With a focused history of patient activities and health symptoms, exposure to a CO source may become apparent. Appropriate and prompt diagnostic testing and treatment are crucial to reduce morbidity and prevent mortality from CO poisoning. Identifying and mitigating the CO source is critical in preventing other poisoning cases.

Recommendations for Clinicians

Consider CO poisoning in patients affected by Hurricane Florence, particularly those in areas currently without power. Assess symptoms and recent patient activities that point to likely CO exposure. Evaluation should also include examination for other conditions, including smoke inhalation, trauma, medical illness, or intoxication.

Administer 100% oxygen until the patient is symptom-free or until a diagnosis of CO poisoning has been ruled out.

Perform COHgb testing when CO poisoning is suspected. Venous or arterial blood may be used for testing. A fingertip pulse multiple wavelength spectrophotometer, or CO-oximeter, can be used to measure heart rate, oxygen saturation, and COHgb levels in the field, but any suspicion of CO poisoning should be confirmed with a COHgb level by multiple wavelength spectrophotometer (CO-oximeter). A conventional two-wavelength pulse oximeter is not accurate when COHgb is present. For more information, see https://www.cdc.gov/disasters/co_guidance.html.

An elevated carboxyhemoglobin (COHgb) level of 2% or higher for non-smokers and 9% or higher COHgb level for smokers strongly supports a diagnosis of CO poisoning. The COHgb level must be interpreted in light of the patient’s exposure history and length of time away from CO exposure, as levels gradually fall once the patient is removed from the exposure. In addition, carbon monoxide can be produced endogenously as a by-product of heme metabolism. Patients with sickle cell disease can have an elevated COHgb level as a result of hemolytic anemia or hemolysis. For additional information about interpretation of COHgb levels, visit https://www.cdc.gov/disasters/co_guidance.html or call Poison Control at (800) 222-1222.

Hyperbaric oxygen therapy (HBO) should be considered in consultation with a toxicologist, hyperbaric oxygen facility, or Poison Control Center (800) 222-1222. For additional management considerations, consult a toxicologist, Poison Control at (800) 222-1222, or a hyperbaric oxygen facility.

Be aware that CO exposure may be ongoing for others spending time in or near the same environment as the patient. These individuals should be evaluated and tested as described in this advisory.

Clinicians treating people for CO poisoning should notify emergency medical services (EMS), the fire department, or law enforcement to investigate and mitigate the source and advise people when it is safe to return.

Advise patients about safe practices related to generators, grills, camp stoves, or other gasoline, propane, natural gas, or charcoal-burning devices. Stress that that these devices should never be used inside an enclosed space, home, basement, garage, or camper — or even outside near an open window or window air conditioner. Please see https://www.cdc.gov/co/pdfs/generators.pdf.